We are performing case-control studies within a population-based registry of children with cerebral palsy (CP) born between 1983- 1985 in four northern California counties, and a cohort of very low birthweight children born 1988-1994. Work during FY98 included: (a) a study of ultramicroassay of blood constituents in newborn infants later recognized to have CP and controls, published October, 1998. This work was done in collaboration with Dr. JM Dambrosia (BFSB) and Dr. TM Phillips of George Washington University. This study observed that mean concentrations of certain cytokines (IL-1,8,9,TNF-a, and RANTES) were higher in every child with CP than in any control, and that other inflammatory cytokines, chemokines, neuropeptides, complement components, thyroid hormones, and coagulation factors differed markedly in children with CP compared with control children. (b) Administration of interferon-alpha for treatment of hemangiomas has apparently provoked spastic diplegia in at least seven children. We observed that neonatal concentrations of interferons identified two levels of expression of a spectrum of inflammatory mediators in a predominantly termborn group of children with CP, one of which was associated with other biochemical and clinical indicators of inflammation, including striking depression of Complement 3 and of triiodothyronine, and included a majority of children with spastic diplegia in this series. This work is compatible with the hypothesis that in addition to other direct and indirect effects of interferons, complement-mediated injury and thyroid hormone related mechanisms may be involved in injury to immature oligodendrocytes and neurons. (c) a paper on criteria for selection of neonates to receive neuroprotective therapies as applied to a population, in press; (f) editorial for BMJ on neonatal encephalopathy and reviews plus addition of our cases relating to antiphospholipid antibodies and the factor V Leiden mutation, under construction.